This main aim of this project is to study the role of the autonomic nervous system in the regulation of energy metabolism in humans and its possible role in the pathophysiology of obesity and type 2 diabetes. We use microneurography to measure muscle sympathetic nerve activity and plasma/urine catecholamines to measure global sympathetic nervous system (SNS)activity. We use fasting and post-prandial pancreatic polypeptide, pupillometry, heart rate/blood pressure tests, and gastric emptying rate to assess parasympathetic nervous system (PNS) activity. In the past year we have established that Pima Indians, especially obese individuals, have a lower SNS and a higher PNS activity compared to Caucasians. As a result, we have 2 main ongoing studies to understand if: a)cortisol (a hormone that inhibits SNS) has a role in the low SNS activity in the Pimas. Preliminary results in 8 Pimas and 15 Caucasians suggest a minor role of cortisol; b)the increased PNS activity explains the hyperinsulinemia that characterizes Pima Indians. Atropine (a drug that blocks PNS) studies have been completed in 4 Caucasians and 5 Pimas.